Dysregulation of Wnt signaling underlies almost all colorectal cancer. A detailed understanding of how the Wnt signal is regulated is therefore of utmost importance in our efforts to develop novel therapies. Casein kinase I isoforms have been shown to be potent positive and negative regulators of the pathway, but the mechanism by which the casein kinase I . (CKI.) isoform functions is not well understood. The data suggest that CKI. is a Wnt-regulated kinase that influences multiple aspects of beta-catenin signaling, but details of this process are sketchy.